In the brain, increased neuronal activity evokes an increase in local cerebral blood flow. This neurovascular coupling is critical to the maintenance of cerebral homeostasis; however, the mechanism by which neuronal activity is communicated to the cerebral microcirculation is unclear. This proposal will investigate the requirement for astrocytic and smooth muscle large conductance calcium-activated potassium (BK) channels in mediating neuronal activity induced vasodilation and regulating vascular tone, respectively. Cortical brain slices will be used to study signaling between neurons, astrocytes and cerebral arterioles in a native cellular context. The mechanisms underlying cytosolic calcium ([Ca2+]c) signal generation in astrocytes will be investigated using confocal imaging. The ability of neurons to signal to arterioles in the absence of BK channel expression will be determined, as measured by vascular diameter and smooth muscle [Ca2+]c changes. Since abnormalities in the cerebral microcirculation have been associated with pathological conditions including stroke and migraine, elucidation of the signaling pathways which dynamically regulate arteriole diameter may aid in the development of novel clinical treatments for such disorders. [unreadable] [unreadable]